Expression and subcellular location of alpha-synuclein during mouse-embryonic development.

ABSTRACT

Alpha-synuclein (alpha-SYN) is one of the major components of intracellular fibrillary aggregates in the brains of a subset of neurodegenerative disorders. Although alpha-SYN expression has been found in developing mouse brain, a detailed distribution during mouse-embryonic development has not been made. Here we describe the expression pattern of alpha-SYN during the development of mice from E9.5 to P0 by immunohistochemistry (IHC). As a result, alpha-SYN was detected as early as E9.5. During the embryonic stages, alpha-SYN was dynamically expressed in several regions of the brain. In the neocortex, expression was detected in the marginal zone (MZ) in the early stages and was later condensed in the MZ and in the subplate (SP); in the cerebellum, expression was initially detected in the deep cerebellar nuclei (DCN) and was later condensed in the Purkinje cells. These spatio-temporal expression patterns matched the neuronal migratory pathways and the formation of the synapse connections. Additionally, alpha-SYN was detected in the sensory systems, including the nasal mucosa, the optic cup, the sensory ganglia, and their dominating nerve fibers. Furthermore, the nuclear location of alpha-SYN protein was found in developing neurons in the early stages, and later it was mostly found in the non-nuclear compartments. This finding was further confirmed by Western blot analysis. These results suggest that alpha-SYN may be involved not only in the migration of neurons and in the synaptogenesis of the central nervous system (CNS) but also in the establishment of the sensory systems. The nuclear location of alpha-SYN may hint at an important function in these events.